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随机命运选择过程中的过渡状态动力学。

Transition state dynamics during a stochastic fate choice.

机构信息

Laboratory for Molecular Cell Biology and Division of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.

Laboratory for Molecular Cell Biology and Division of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK

出版信息

Development. 2019 Apr 8;146(12):dev173740. doi: 10.1242/dev.173740.

Abstract

The generation of multiple fates from a uniform cell population via self-organisation is a recurring feature in development and regeneration. However, for most self-organising systems, we have little understanding of the processes that allow cells to become different. One of the clearest examples of developmental self-organisation is shown by , with cells segregating into two major fates, stalk and spore, within multicellular aggregates. To characterise the gene expression decisions that underlie this cell fate bifurcation, we carried out single cell transcriptomics on aggregates. Our data show the transition of progenitors into prespore and prestalk cells occurs via distinct developmental intermediates. Few cells were captured switching between states, with minimal overlap in fate marker expression between cell types, suggesting states are discrete and transitions rapid. Surprisingly, fate-specific transcript dynamics were a small proportion of overall gene expression changes, with transcript divergence coinciding precisely with large-scale remodelling of the transcriptome shared by prestalk and prespore cells. These observations suggest the stepwise separation of cell identity is temporally coupled to global expression transitions common to both fates.

摘要

通过自组织从均匀的细胞群体中产生多种命运是发育和再生中的一个反复出现的特征。然而,对于大多数自组织系统,我们对允许细胞变得不同的过程知之甚少。发育自组织的一个最明显的例子是由 展示的,其中细胞在多细胞聚集体中分离成两个主要命运,柄和孢子。为了描述这种细胞命运分岔的基因表达决策,我们对 聚集体进行了单细胞转录组学分析。我们的数据表明,前孢子和前柄细胞的祖细胞通过不同的发育中间体过渡。很少有细胞在状态之间切换,细胞类型之间命运标记表达的重叠很少,这表明状态是离散的,过渡是迅速的。令人惊讶的是,命运特异性转录动力学只是总基因表达变化的一小部分,转录分歧与前孢子和前柄细胞共享的转录组的大规模重塑完全吻合。这些观察结果表明,细胞身份的逐步分离在时间上与两种命运共有的全局表达转变相关。

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本文引用的文献

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Cell Cycle Heterogeneity Can Generate Robust Cell Type Proportioning.细胞周期异质性能够产生稳健的细胞类型比例。
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